Stress, and the inability to escape stress, is a factor that may disproportionately affect minority populations. Stress has a major impact on substance and alcohol abuse. Stress also increases drug craving associated with recidivism, which is of major concern in treatment of drug abuse victims. Very recent evidence has suggested that the CB1 cannabinoid receptor and endogenous cannabinoids are key components in the craving associated with hedonic alcohol intake and overeating. The Research Core-Drug Abuse will investigate the functional genomics of stress and the cannabinoid and opioid systems in cellular adaptations to substance abuse. Aims will include: Aim 1: To investigate proenkephalin and prodynorphin gene expression and enkephalin and dynorphin peptide production in response to drug treatments or stress as a function of the genomic differences between wildtype and homozygous transgenic mice deficient in CB1 cannabinoid receptors or modified in fosB or CREB production. This aim is under the direction of Dr. Steve Franklin, JLC-BBRI Research Staff and Assoc. Professor of Chemistry at NCCU. Aim 2: To investigate the influence of prior drug exposure or stress on reinforcement effects of and antinociception in response to opioid drugs as a function of the genomic differences between wildtype and homozygous transgenic mice deficient in the CB1 cannabinoid receptor or modified in fosB or CREB production. These behavioral studies oftransgenic mice will be conducted in collaboration with Dr. Linda Dykstra, Professor of Psychology at University of North Carolina at Chapel Hill. Aim 3: Search for unique geue expression in response to opioid, cannabinoid and glucocorticoid treatment in neuronal cultures and b. drugs of abuse and stress in mesolimbic brain in mice. These studies will utilize cDNA hybridization microarray technology in collaboration with Dr. Kent Vrana of the Functional Genomics Group at Wake Forest University School of Medicine.